COMBIVIR 150 MG/300 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Combivir 150 mg/300 mg film-coated tablets

lamivudine/zidovudine

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Combivir and what is it used for
2. What you need to know before you take Combivir
3. How to take Combivir
4. Possible side effects
5. Storing Combivir
6. Contents of the pack and other information

1. What is Combivir and what is it used for

Combivir is used to treat HIV infection in adults and children.

Combivir contains two active substances that are used to treat HIV infection: lamivudine and zidovudine. Both belong to a group of medicines called nucleoside analogue reverse transcriptase inhibitors (NRTIs).

Combivir does not completely cure HIV infection; it reduces the amount of virus in your body and keeps it at a low level. It also increases the number of CD4 cells in your blood. CD4 cells are a type of white blood cell that plays an important role in helping your body fight infection.

Not everyone responds to treatment with Combivir in the same way. Your doctor will monitor the effectiveness of your treatment.

2. What you need to know before you take Combivir

Do not take Combivir

• if you are allergicto lamivudine, zidovudine or any of the other ingredients of this medicine (listed in section 6)
• if you have very low red blood cell count(anaemia) or very low white blood cell count(neutropenia).

Consult your doctorif you think you may have any of these conditions.

Be especially careful with Combivir

Some people who take Combivir or other HIV treatments have a higher risk of serious side effects. You need to know that there is a higher risk:

• if you have ever had liver disease, including hepatitis B or C (if you have hepatitis B, do not stop taking Combivir without your doctor's advice, as it may get worse)
• if you have kidney disease
• if you have significant overweight(especially if you are a woman).

Consult your doctor ifyou have any of these conditions.Your doctor will decide if the active substances are suitable for you. You may need to have extra tests, including blood tests, while taking this medicine. For more information, see section 4.

Be aware of important symptoms

Some people who take HIV medicines develop other conditions, which can be serious. You need to know what important signs and symptoms to look out for while taking Combivir.

Read the information on “Other possible side effects of HIV treatment” in section 4 of this leaflet.

Other medicines and Combivir

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines,including herbal medicines and those bought without a prescription.

Remember to tell your doctor or pharmacist if you start taking any new medicine while taking Combivir.

The following medicines must not be used with Combivir:

• other medicines that contain lamivudine, used to treat HIV infectionor hepatitis B
• emtricitabine, to treat HIV infection
• stavudine, to treat HIV infection
• ribavirin or ganciclovir injections, to treat viral infections
• high doses of co-trimoxazole(a combination of trimethoprim and sulfamethoxazole), an antibiotic
• cladribine, used to treat hairy cell leukaemia.

Tell your doctorif you are being treated with any of these medicines.

Some medicines may increase the risk of side effects, or make side effects worse.

These include:

• valproic acid, to treat epilepsy
• interferon, to treat viral infections
• pyrimethamine, to treat malariaand other parasitic infections
• dapsone, to prevent neumoniaand treat skin infections
• fluconazole or flucytosine, to treat fungal infectionssuch as Candida
• pentamidine or atovaquone, to treat parasitic infections such as Pneumocystis jiroveciipneumonia (often referred to as PCP)
• amphotericin or co-trimoxazole (a combination of trimethoprim and sulfamethoxazole), to treat fungal and bacterial infections
• probenecid, to treat goutand similar conditions, and given with some antibiotics to make them more effective
• methadone, used as a heroin substitute
• vincristine, vinblastine or doxorubicin, to treat cancer.

Tell your doctorif you are taking any of these medicines.

Some medicines interact with Combivir

These include:

• clarithromycin, an antibiotic

If you are taking clarithromycin, take your dose at least 2 hours before or after taking Combivir.

• phenytoin, to treat epilepsy.

Tell your doctorif you are taking phenytoin. Your doctor may need to monitor you while you are taking Combivir.

• medicines (usually liquids) that contain sorbitol and other polyalcohols(such as xylitol, mannitol, lactitol or maltitol) if taken regularly.

Tell your doctor or pharmacistif you are being treated with any of these.

Pregnancy

If you are pregnant, if you become pregnant, or if you are planning to become pregnant, talk to your doctor about the risks and benefits of taking Combivir for both you and your baby.

Combivir and similar medicines may cause side effects in babies during pregnancy.

If you have been taking Combivir during your pregnancy, your doctor may ask you to have regular blood tests and other diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs during pregnancy, the benefit of protection against HIV was greater than the risk of side effects.

Breast-feeding

It is not recommendedthat women with HIV breast-feed their babies because HIV infection can be passed to the baby through breast milk.

A small amount of the ingredients of Combivir may also pass into breast milk.

If you are breast-feeding or thinking of breast-feeding, consult your doctor as soon as possible.

Driving and using machines

Combivir may cause dizzinessand have other side effects that reduce your alertness.

Do not drive or operate machineryunless you feel well.

Combivir contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is, essentially “sodium-free”.

3. How to take Combivir

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

Swallow the Combivir tablets with a little water. Combivir can be taken with or without food.

If you cannot swallow the tablets whole, you can break them and mix with a small amount of food or drink; take the whole dose immediately.

Stay in regular contact with your doctor

Combivir helps to control your condition. You need to take it every day to control your illness. You may still develop other infections and illnesses associated with HIV.

Stay in touch with your doctor and do not stop taking Combivirwithout talking to your doctor first.

How much to take

Adults and adolescents weighing at least30 kg

The usual dose of Combivir is one tablet twice a day.

Take the tablets at regular intervals, leaving approximately 12 hours between each tablet.

Children weighing between 21 and30 kg

The usual starting dose is half a tablet (½) in the morning and one whole tablet in the evening.

Children weighing between 14 and21 kg

The usual starting dose is half a tablet (½) in the morning and half a tablet (½) in the evening.

For children weighing less than 14 kg, lamivudine and zidovudine (the active substances of Combivir) should be taken separately.

If you take more Combivir than you should

If you accidentally take more Combivir than you should, tell your doctor or pharmacist, or contact the emergency department of your nearest hospital for advice.

If you forget to take Combivir

If you forget to take a dose, take it as soon as you remember and then continue with your normal treatment schedule. Do not take a double dose to make up for forgotten doses.

4. Possible Adverse Effects

During HIV treatment, there may be an increase in weight and levels of glucose and lipids in the blood. This may be partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to HIV medications themselves. Your doctor will monitor these changes.

Treatment with Combivir often causes a loss of fat from the legs, arms, and face (lipoatrophy). This loss of body fat has been shown to be not completely reversible after stopping zidovudine. Your doctor should monitor signs of lipoatrophy. If you notice any fat loss in your legs, arms, and face, inform your doctor. When these symptoms occur, Combivir should be discontinued and HIV treatment changed. Like all medications, this medication can produce adverse effects, although not all people suffer from them.

When you are undergoing HIV treatment, it can be difficult to distinguish whether a symptom is an adverse effect of Combivir or other medications you are taking, or is due to an effect of the HIV disease itself. Therefore, it is very important that you inform your doctor about any change in your health.

In addition to the adverse effects listed below for Combivir, other disorders can develop during combined HIV treatment.

It is essential that you read the information under the heading “Other possible adverse effects of combined HIV treatment”.

Very Common Adverse Effects

May affect more than 1 in 10people:

• headache
• discomfort (nausea).

Common Adverse Effects

May affect up to 1 in 10people:

• vomiting
• diarrhea
• stomach pain
• loss of appetite
• feeling of dizziness
• fatigue, lack of energy
• fever (high temperature)
• feeling of general discomfort
• difficulty sleeping (insomnia)
• muscle pain and discomfort
• joint pain
• cough
• irritated nose or excessive nasal secretion
• skin rash
• hair loss (alopecia).

Common adverse effects that may appear in blood tests are:

• low red blood cell count (anemia)or low white blood cell count (neutropenia or leucopenia)
• increase in liver enzyme levels
• increase in bilirubin levels in the blood (a substance produced by the liver) that can cause a yellowish color of the skin.

Uncommon Adverse Effects

May affect up to 1 in 100people:

• difficulty breathing
• gas (flatulence)
• itching
• muscle weakness.

Uncommon adverse effects that may appear in blood tests are:

• a decrease in the number of cells involved in blood clotting (thrombocytopenia)or in all classes of blood cells (pancytopenia).

Rare Adverse Effects

May affect up to 1 in 1,000people:

• severe allergic reaction that causes swelling of the face, tongue, or throat, which can cause difficulty swallowing or breathing

• liver disorders, such as jaundice, increased liver size, fatty liver, inflammation (hepatitis)
• lactic acidosis (excess of lactic acid in the blood, see the section below “Other possible adverse effects of combined HIV treatment”)
• pancreatitis (inflammation of the pancreas)
• chest pain, heart muscle disease (myocardial disease)
• seizures (convulsions)
• feeling of depression or anxiety, difficulty concentrating, drowsiness
• indigestion, taste disorders
• changes in nail color, skin, or mucous membranes inside the mouth
• flu-like symptoms — chills and sweating
• tingling sensation on the skin (pins and needles)
• feeling of weakness in the limbs
• muscle tissue rupture
• numbness
• frequent urination
• breast enlargement in men.

Rare adverse effects that may appear in blood tests are:

• increase in an enzyme called amylase
• bone marrow failure to produce new red blood cells (pure red cell aplasia).

Very Rare Adverse Effects

May affect up to 1 in 10,000people:

A very rare adverse effect that may appear in blood tests is:

• bone marrow failure to produce new red or white blood cells (aplastic anemia).

If you experience adverse effects

Inform your doctor or pharmacistif you consider that any of the adverse effects you are experiencing is serious or if you notice any adverse effect not mentioned in this leaflet.

Other possible adverse effects of combined HIV treatment

Combined treatments, like Combivir, can cause other disorders to develop during HIV treatment.

Exacerbation of old infections

People with advanced HIV infection (AIDS) have weakened immune systems and are more likely to suffer from severe infections (opportunistic infections). When these people start treatment, they may find that old, hidden infections flare up, causing signs and symptoms of inflammation. These symptoms are probably due to an improvement in the body's immune response, which allows it to fight these infections.

In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) can also appear after you have started taking medications for your HIV infection. Autoimmune disorders can appear many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness that starts in the hands and feet and moves up to the torso, palpitations, tremors, or hyperactivity; inform your doctor immediately to receive the necessary treatment.

If you notice any symptoms of infection while taking Combivir:

Inform your doctor immediately. Do not take any other medication for the infection without your doctor's advice.

Lactic acidosis is a rare but serious adverse effect

Some people taking Combivir develop a disorder called lactic acidosis, along with an increase in liver size.

Lactic acidosis is due to an increase in lactic acid levels in the body. It is rare, and if it occurs, it usually develops after a few months of treatment. It can be potentially fatal, causing failure of internal organs. Lactic acidosis is more likely to develop in patients with liver disease or in obese people (with significant overweight), especially women.

Signs of lactic acidosis include:

• difficulty breathing, rapid and deep breathing
• drowsiness
• numbness or weakness of the limbs
• discomfort (nausea), vomiting
• stomach pain.

During your treatment, your doctor will monitor any signs that may indicate you are developing lactic acidosis. If you notice any of the symptoms mentioned above or are concerned about any other symptom:

See your doctor as soon as possible.

You may have bone problems

Some people receiving combined HIV treatment may develop a bone disease called osteonecrosis. With this disease, part of the bone tissue dies due to a reduction in blood supply to the bone. People are more likely to suffer from this disease:

• if they have been taking combined treatment for a long time
• if they also take anti-inflammatory medications called corticosteroids
• if they drink alcohol
• if their immune system is severely weakened
• if they are overweight.

Signs of osteonecrosis include:

• stiffness in the joints
• pain and discomfort (especially in the hip, knee, and shoulder)
• difficulty moving.

If you notice any of these symptoms:

Inform your doctor.

Other effects that may appear in blood tests

Combined HIV treatment can also cause:

• an increase in lactic acid levels in the blood, which can rarely lead to lactic acidosis.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Combivir

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the carton.

Do not store above 30°C.

Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package contents and additional information

Composition of Combivir

The active ingredients are lamivudine and zidovudine. The other ingredients are:

• core of the tablet: microcrystalline cellulose, sodium carboxymethyl starch (gluten-free), magnesium stearate, colloidal silicon dioxide
• • coating: hypromellose, titanium dioxide, macrogol 400, and polysorbate 80.

Appearance of Combivir and package contents

Combivir film-coated tablets are supplied in cardboard cartons containing blister packs or a bottle with a child-resistant closure. Each type of packaging contains 60 film-coated tablets. These tablets are white to off-white, capsule-shaped, scored, and have the code GXFC3 engraved on both sides.

Marketing authorization holder and manufacturer

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Detailed information on this medication is available on the European Medicines Agency website http://www.ema.europa.eu